Chronic lung diseases are associated with gene expression programs favoring SARS-CoV-2 entry and severity
Linh T. Bui, Nichelle I. Winters, Mei-I Chung, Chitra Joseph, Austin J. Gutierrez, Arun C. Habermann, Taylor Adams, Jonas C. Schupp, Sergio Poli, Lance Peter, Chase J. Taylor, Jessica B. Blackburn, Bradley W. Richmond, Andrew G. Nicholson, Doris M. Rassl, William Wallace, Iván O. Rosas, Gísli Jenkins, Naftali Kaminski, Jonathan A. Kropski, Nicholas E. Banovich, Human Cell Atlas Lung Biological Network, Alexander V. Misharin, Alexander M. Tsankov, Avrum Spira, Pascal Barbry, Alvis Brāzma, Christos Samakovlis, Douglas P. Shepherd, Emma L. Rawlins, Fabian J. Theis, Jennifer Griffonnet, Haeock Lee, Herbert B. Schiller, Paul Hofman, Joseph E. Powell, Joachim L. Schultze, Jeffrey A. Whitsett, Jiyeon Choi, Joakim Lundeberg, Naftali Kaminski, Jonathan A. Kropski, Nicholas E. Banovich, José Ordovás-Montañés, Jayaraj Rajagopal, Kerstin B. Meyer, Mark A. Krasnow, Kourosh Saeb‐Parsy, Kun Zhang, Robert Lafyatis, Sylvie Leroy, Muzlifah Haniffa, Martijn C. Nawijn, Marko Nikolić, Maarten van den Berge, Malte Kühnemund, Charles‐Hugo Marquette, Michael von Papen, Oliver Eickelberg, Orit Rosenblatt-Rosen, Paul A. Reyfman, Dana Pe’er, Péter Horváth, Purushothama Rao Tata, Aviv Regev, Mauricio Rojas, Max A. Seibold, Alex K. Shalek, Jason R. Spence, Sarah A. Teichmann, Stephen R. Quake, Thu Elizabeth Duong, Tommaso Biancalani, Tushar Desai, Xin Sun, Laure‐Emmanuelle Zaragosi
Abstract
Patients with chronic lung disease (CLD) have an increased risk for severe coronavirus disease-19 (COVID-19) and poor outcomes. Here, we analyze the transcriptomes of 611,398 single cells isolated from healthy and CLD lungs to identify molecular characteristics of lung cells that may account for worse COVID-19 outcomes in patients with chronic lung diseases. We observe a similar cellular distribution and relative expression of SARS-CoV-2 entry factors in control and CLD lungs. CLD AT2 cells express higher levels of genes linked directly to the efficiency of viral replication and the innate immune response. Additionally, we identify basal differences in inflammatory gene expression programs that highlight how CLD alters the inflammatory microenvironment encountered upon viral exposure to the peripheral lung. Our study indicates that CLD is accompanied by changes in cell-type-specific gene expression programs that prime the lung epithelium for and influence the innate and adaptive immune responses to SARS-CoV-2 infection.